PMID- 16228231
OWN - NLM
STAT- MEDLINE
DCOM- 20060627
LR  - 20131121
IS  - 0302-766X (Print)
IS  - 0302-766X (Linking)
VI  - 323
IP  - 2
DP  - 2006 Feb
TI  - Fibroblast growth factor 2 facilitates the differentiation of transplanted bone 
      marrow cells into hepatocytes.
PG  - 221-31
AB  - We have developed an in vivo mouse model, the green fluorescent protein 
      (GFP)/carbon tetrachloride (CCl(4)) model, and have previously reported that 
      transplanted GFP-positive bone marrow cells (BMCs) differentiate into hepatocytes 
      via hepatoblast intermediates. Here, we have investigated the growth factors that 
      are closely related to the differentiation of transplanted BMCs into hepatocytes, 
      and the way that a specific growth factor affects the differentiation process in 
      the GFP/CCl(4) model. We performed immunohistochemical analysis to identify an 
      important growth factor in our model, viz., fibroblast growth factor (FGF). In 
      liver samples, the expression of FGF1 and FGF2 and of FGF receptors (FGFRs; 
      FGFR1, FGFR2) was significantly elevated with time after bone marrow 
      transplantation (BMT) compared with other factors, and co-expression of GFP and 
      FGFs or FGFRs could be detected. We then analyzed the effect and molecular 
      mechanism of FGF signaling on the enhancement of BMC differentiation into 
      hepatocytes by immunohistochemistry, immunoblotting, and microarray analysis. 
      Treatment with recombinant FGF (rFGF), especially rFGF2, elevated the 
      repopulation rate of GFP-positive cells in the liver and significantly increased 
      the expression of both Liv2 (hepatoblast marker) and albumin (hepatocyte marker). 
      Administration of rFGF2 at BMT also raised serum albumin levels and improved the 
      survival rate. Transplantation of BMCs with rFGF2 specifically activated tumor 
      necrosis factor-alpha (TNF-alpha) signaling. Thus, FGF2 facilitates the 
      differentiation of transplanted BMCs into albumin-producing hepatocytes via 
      Liv2-positive hepatoblast intermediates through the activation of TNF-alpha 
      signaling. Administration of FGF2 in combination with BMT improves the liver 
      function and prognosis of mice with CCl(4)-induced liver damage.
FAU - Ishikawa, Tsuyoshi
AU  - Ishikawa T
AD  - Department of Molecular Science and Applied Medicine (Gastroenterology and 
      Hepatology), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, 
      755-8505 Yamaguchi, Japan.
FAU - Terai, Shuji
AU  - Terai S
FAU - Urata, Yohei
AU  - Urata Y
FAU - Marumoto, Yoshio
AU  - Marumoto Y
FAU - Aoyama, Koji
AU  - Aoyama K
FAU - Sakaida, Isao
AU  - Sakaida I
FAU - Murata, Tomoaki
AU  - Murata T
FAU - Nishina, Hiroshi
AU  - Nishina H
FAU - Shinoda, Koh
AU  - Shinoda K
FAU - Uchimura, Shunji
AU  - Uchimura S
FAU - Hamamoto, Yoshihiko
AU  - Hamamoto Y
FAU - Okita, Kiwamu
AU  - Okita K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051014
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/drug effects/*metabolism
MH  - *Bone Marrow Transplantation
MH  - Carbon Tetrachloride/toxicity
MH  - Cell Differentiation/drug effects/*physiology
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblast Growth Factor 2/*physiology
MH  - Green Fluorescent Proteins/metabolism
MH  - Hepatocytes/*cytology/drug effects/metabolism
MH  - Immunohistochemistry
MH  - Liver Cirrhosis, Experimental/chemically induced
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins
MH  - Signal Transduction
EDAT- 2005/10/18 09:00
MHDA- 2006/06/28 09:00
CRDT- 2005/10/18 09:00
PHST- 2005/05/25 00:00 [received]
PHST- 2005/08/09 00:00 [accepted]
PHST- 2005/10/18 09:00 [pubmed]
PHST- 2006/06/28 09:00 [medline]
PHST- 2005/10/18 09:00 [entrez]
AID - 10.1007/s00441-005-0077-0 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2006 Feb;323(2):221-31. doi: 10.1007/s00441-005-0077-0. Epub 
      2005 Oct 14.